Altered Recruitment of Motor Cortex Neuronal Activity During the Grasping Phase of Skilled Reaching in a Chronic Rat Model of Unilateral Parkinsonism

Abstract

Parkinson's disease causes prominent difficulties in the generation and execution of voluntary limb movements, including regulation of distal muscles and coordination of proximal and distal movement components to achieve accurate grasping. Difficulties with manual dexterity have a major impact on activities of daily living. We used extracellular single neuron recordings to investigate the neural underpinnings of parkinsonian movement deficits in the motor cortex of chronic unilateral 6-hydroxydopamine lesion male rats performing a skilled reach-to-grasp task the. Both normal movements and parkinsonian deficits in this task have striking homology to human performance. In lesioned animals there were several differences in the activity of cortical neurons during reaches by the affected limb compared with control rats. These included an increase in proportions of neurons showing rate decreases, along with increased amplitude of their average rate-decrease response at specific times during the reach, suggesting a shift in the balance of net excitation and inhibition of cortical neurons; a significant increase in the duration of rate-increase responses, which could result from reduced coupling of cortical activity to specific movement components; and changes in the timing and incidence of neurons with pure rate-increase or biphasic responses, particularly at the end of reach when grasping would normally be occurring. The changes in cortical activity may account for the deficits that occur in skilled distal motor control following dopamine depletion, and highlight the need for treatment strategies targeted toward modulating cortical mechanisms for fine distal motor control in patients.

Intrinsic Disruption of the M1 Cortical Network in a Mouse Model of Parkinson's Disease

“…Consistent with the involvement of M1 in the pathogenesis of PD, previous studies have described various abnormalities in the M1 of parkinsonian patients and PD models, including increased beta activity of local field potentials and electroencephalogram, 14,30,[41][42][43][44][45][46][47] attenuated motor parameter encoding and increased pairwise synchronization of M1 neurons in MPTPtreated monkeys, 16,35,36,[48][49][50][51] as well as functional imaging abnormalities in the M1 of PD patients. 52 At the population level M1 can be regarded as a dynamic system generating temporally precise sequences of output motor commands in layer 5 PT neurons to control dexterous movements.…”

Evolution of Gross Forelimb and Fine Digit Kinematics during Skilled Reaching Acquisition in Rats

“…One candidate is differences in dopamine signaling/receptor profiles, as dopamine plays an important role in motor adaptation ( Panigrahi et al, 2015 ; Bova et al, 2020 ). Other possibilities include differences in cortical plasticity ( Li et al, 2017 ; Hyland et al, 2019 ) and corticostriatal coherence ( Lemke et al, 2019 ).…”

Precisely timed dopamine signals establish distinct kinematic representations of skilled movements

“…In skilled reaching, rats learn the coordinated forelimb and digit movements to reach for, grasp, and consume sugar pellets. Skilled reaching is readily learned by rats over several sessions ( Klein et al, 2012 ; Lemke et al, 2019 ), requires precise coordination between the forelimb and digits, and is sensitive to dopamine depletion ( Hyland et al, 2019 ; Whishaw et al, 1986 ). It is therefore an excellent model for assessing dopaminergic contributions to dexterous skill.…”